Aerosol formulations are employed in respiratory therapy for the topical administration of medication to the mucosal linings of the tracheobronchial tree. The term aerosol describes a nebulized solution consisting of very fine particles carried by a gas (usually air) to the site of therapeutic application. When the site of application is the alveoli and small bronchioles, the medicament must be dispersed as droplets of roughly 5 micron diameter. When the target is the nasal and pharyngeal region, larger droplets are appropriate. Conditions susceptible to treatment with aerosols include bronchospasms, loss of compliance, mucosal edema, pulmonary infections and the like.
Solutions of medicament in buffered saline and similar vehicles are commonly employed to generate an aerosol in a nebulizer. Within the container of a conventional air-driven nebulizer is a small unit that produces aerosolized droplets inside the flask. The walls of the flask act as a baffle removing large droplets from the mist. The large droplets run down the wall and drop back into the reservoir, leaving a mist of small droplets that can penetrate into the lung. A current of air or oxygen carries the fine mist through the large outlet tube of the nebulizer. Simple nebulizers operate on Bernoulli's principle and employ a stream of air or oxygen to generate the spray particles. More complex nebulizers employ ultrasound to create the spray particles. Both types are well known in the art and are described in standard textbooks of pharmacy such as Sprowls'American Pharmacy and Remington's The Science and Practice of Pharmacy. Other devices for generating aerosols employ compressed gases, usually hydrofluorocarbons and chlorofluorocarbons, which are mixed with the medicament and any necessary excipients in a pressurized container; these devices are likewise described in standard textbooks such as Sprowls and Remington. Because all nebulizers require a fluid medium for the development of the aerosol spray, and because the spray is to be inspired directly into the lung, water is the only vehicle that can reasonably be employed. A problem thus arises when the medicament is itself not sufficiently stable in an aqueous environment to provide a practical shelf life for the aqueous formulation.
Various methods have been tried to circumvent this problem. It is known in the art to prepare and maintain the aqueous solution or suspension at a reduced temperature. This approach has two drawbacks: first, storage becomes expensive and bothersome; and second, the degradative processes are slowed, but they are not stopped.
An alternative to refrigerating a solution or suspension that has already been prepared is to make up the medicament solution immediately before use. However, the accurate and sterile transfer of the medicament into the carrier is generally only practical when the medicament is provided as a solution in another (non-aqueous) solvent. The formulations chemist is then faced with the problem of devising not just one, but two stable, compatible formulations.
Therefore, it would be highly desirable to have a system for generating water-based aerosols from water-sensitive medicaments without the need for refrigeration. This need is satisfied, the limitations of the prior art overcome, and other benefits realized in accordance with the principles of the present invention.